In the acutely agitated manic patient, adjuncts to lithium are frequently employed. For several decades the most popular adjuncts have been neuroleptics. The side effects, some life threatening, some disabling, make the decision to employ neuroleptics one with significant disadvantages to balance against the benefits. It has been reported that the benzodiazepine lorazepam is efficacious in the adjunctive treatment of mania, but there has been only one small double-blind comparison of benzodiazepine versus neuroleptics. While the limited number of patients studied prevented the authors from making definitive conclusions about the relative efficacy of these two medication classes, it was demonstrated that this type of study is feasible. Our pilot data confirm this feasibility. The proposed study would be designed to compare, in a double-blind fashion, the benzodiazepine lorazepam, with the neuroleptic perphenazine, as adjuncts to lithium in the treatment of acute mania. We propose to focus of those patients most in need of adjunctive medication-the agitated acutely manic patient. We will operationalize agitation using an expanded BPRS-derived agitation subscale and employ a threshold agitation severity criterion for enrollment into the study. Inpatients of both genders between the ages of 18 and 65 with a diagnosis of mania or mixed manic episode will be eligible for participation in the study until a total of 50 patients have entered the protocol. Over a three week period, hospitalized manic patients will receive lithium and, in a double-blind fashion, either lorazepam or perphenazine. Safety and tolerance of medications will be assessed through daily close monitoring of symptoms and twice daily vital signs. Efficacy will be addressed through daily evaluation with an expanded Brief Psychiatric Rating Scale (BPRS), a sedation scale, and standardized nursing observations every shift. The young Mania Scale and the modified Simpson Angus Scale for Extrapyramidal Side Effects will be administered every three days. Information will also be collected on the length of hospitalization, total doses of adjunctive medication, use of restraints (both the number of restraint episodes and duration), the amount of time that a patient requires individual staff observation, and the time taken for the patient to advance through the ward's status system.